1. Field of the Invention
This invention relates to a pharmaceutical for treating cancer and, more particularly, to a plurality of thioxanthone ring system derivatives and pharmaceutical composition comprising the same.
2. Description of the Related Art
The main reasons of cancer are due to the unusual pathological changes of cells or unnormal proliferation. The tumor means the cell aggregated to form the phyma. There are two types of tumors: benign tumors and malignant tumors. Generally, the growing rate of benign tumors is slower and the tumors will not affect the neighbor normal tissue as well as it is not lethality. Most of them can be excised by surgery unless they grow on a vital part and relapse. Malignant tumors are generally called cancer, and the proliferation of cancer cell will invade peripheral tissues, moreover, the proliferation of cancer cell will transfer through Circulatory System or Lymphatic system. The tumor comprises solid tumor and non-solid tumor. The cancer caused by the solid tumor comprises lung cancer, colorectal cancer, central nervous system cancer, melanoma, ovarian cancer, prostate cancer, kidney cancer, breast cancer, small cell cervical cancer, gastric cancer, cervical cancer, osteosarcoma . . . etc. The cancer caused by the non-solid tumor comprises is Leukemia, lymphoma cancer, multiple myeloma . . . etc.
Generally, the method for treating cancer can be separated into three kinds: surgery, radiation therapy and chemotherapy. And then, the appropriate method is decided upon the position of tumor and the status of the patient. In recent years, some new methods for treating cancer cell are disclosed, for example, gene therapy, molecular targeted therapies, antigenic therapy.
In recent years, the medical research finds that chronic inflammation will result in a chronic disease, such as cancer, diabetes mellitus . . . etc. Therefore, it points out that anthraquinone derivatives such as spiro-thioxanthene and spiro-xanthene-9,2-[1,3,4]-thiadiazole can inhibit human's inflammation (H. N. Hafez et al. Bioorganic & Medicinal Chemistry Letters, 2008, 18). Furthermore, it also points out anthraquinone derivatives such as 6-[[(Diphenylmethylene)amino]oxy]hexanoic Acid can cure Diabetes mellitus (D. Rakowitz et al. Arch. Pharm. Chem. Life Sci. 2007).
In addition, duplicating and maintaining the length of the telomere, which is located at the end of a chromosome, must rely on telomerase. A lot of research points out that the telomerase activity is rarely detected in normal human somatic cells, but is usually detected in the cells that keep proliferating, such as hematopoietic cells, embryogenic cells, stem cells, germ cell, immortalized cell, tumor cells, etc. Therefore, in normal somatic cells, the telomere gets shortened at each time of cell mitosis. When the telomere is shortened to some level, the cell will lose the ability of replication and go into apoptosis stage, and this stage is also called M1 stage (mortality stage 1).
In the M1 stage, tumor suppressor gene of the cells mutate as p53 and Rb to make the cells leave the M1 stage and keep processing cell mitosis. The above situation is called M2 stage (mortality stage 2). In M2 stage, the telomerase activity doesn't exist so that the length of the telomere will shorten to result in the instability of the chromosome. Therefore, the signal transduction of the cells cannot perform result in the death of the cells. According to the abovementioned, the M2 stage is also called crisis, and most cells will died during the M2 stage. However, few cells will survive due to the telomerase activity, and the few cells will keep processing the cell mitosis to turn into the immortalized cells or the tumor cells.
Because the telomerase activity is rarely detected in normal human somatic cells, but is usually detected in the tumor cells so that the telomerase becomes the newly objective of the related research about the target therapy.
In some cells, which quickly proliferate and grow, its supercoiled structure needs to be entangled and disentangled for processing DNA transcription and translation so that topoisomerase, which is responsible for the abovementioned actions, is a newly objective for target therapy. The abovementioned objective is used to maintain a break portion while DNA disentangles for inhibiting the cancer cells. The inhibition mechanism of the topoisomerase has three types illustrated as follows. The first type is that drugs combines with DNA fragment, and then the topoisomerase II combines with the complex formed by the drugs and DNA. The second type is that the topoisomerase II combines with DNA fragment first, and then the drugs combines with the complex formed by the topoisomerase II and DNA. The last type is that the drugs will combines with the topoisomerase II, and then the complex formed by the drugs and the topoisomerase II will combines with the DNA fragment. To sum up the above three types, ternary complex including the topoisomerase, the drugs and the DNA fragment will be formed. The main mechanism of the abovementioned action is that DNA stands are first broken by the topoisomerase. And then, the complex composed of the topoisomerase and the drugs will fix on the DNA. Because the broken DNA cannot combine again so that the enzyme cannot act. Therefore, it will be determined that DNA is broken to result in the death of the cells. Some anti-cancer drugs, such as doxorubicin and mitoxantrone, reach the good effect for curing cancer by inhibiting the topoisomerase.